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. 2000 Jun;78(6):2878–2891. doi: 10.1016/S0006-3495(00)76829-9

Neuronal death and perinatal lethality in voltage-gated sodium channel alpha(II)-deficient mice.

R Planells-Cases 1, M Caprini 1, J Zhang 1, E M Rockenstein 1, R R Rivera 1, C Murre 1, E Masliah 1, M Montal 1
PMCID: PMC1300874  PMID: 10827969

Abstract

Neural activity is crucial for cell survival and fine patterning of neuronal connectivity during neurodevelopment. To investigate the role in vivo of sodium channels (NaCh) in these processes, we generated knockout mice deficient in brain NaChalpha(II). NaChalpha(II)(-/-) mice were morphologically and organogenically indistinguishable from their NaChalpha(+/-) littermates. Notwithstanding, NaChalpha(II)(-/-) mice died perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of NaChalpha(II)(-/-) mice were sharply attenuated. Death appears to arise from severe hypoxia consequent to the brainstem deficiency of NaChalpha(II). NaChalpha(II) expression is, therefore, redundant for embryonic development but essential for postnatal survival.

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